Is DNAH10 p.Ile4530Phe (c.13588A>T) pathogenic?

DNAH10 p.Ile4530Phe (c.13588A>T) is classified Uncertain significance in DNAH10 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-08). AlphaMissense: likely pathogenic (0.7062); Very rare (popmax 0.00133%, afr).

How common is DNAH10 p.Ile4530Phe (c.13588A>T) in the general population?

DNAH10 p.Ile4530Phe (c.13588A>T) is very rare (popmax 0.00133%, afr) (gnomAD).

What do computational predictors say about DNAH10 p.Ile4530Phe (c.13588A>T)?

AlphaMissense predicts likely pathogenic (score 0.7062) — an in-silico prediction, not a clinical call.

DNAH10 p.Ile4530Phe

c.13588A>T · rs1955406222 · VCV3083436

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7062 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Missense predictors

1/2 damaging

AlphaMissense, REVEL

Computational evidence

Protein change
AlphaMissense	0.7062	likely pathogenic
REVEL	0.217	benign-leaning
⇒ AlphaMissense calls this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.9	GERP 0.75, phastCons 1
Overall
CADD	19.43	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM I4412F vs ClinVar I4530F) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00133% African / African-American · 1/74,916 alleles

Overall 0.000657% 1/152,186 alleles · very rare

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: DNAH10
Protein: p.Ile4530Phe
Coding: c.13588A>T
MANE Select: NM_001372106
dbSNP: rs1955406222
Type: single nucleotide variant
Location: chr12:123934731 (GRCh38)
Gene constraint: LOEUF 0.763 · pLI <0.01 (gnomAD)

Full DNAH10 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DNAH10 p.Ala2444Val Uncertain significance ★★ ⚠ same type
DNAH10 p.Arg2111Trp Uncertain significance ★★ ⚠ same type
DNAH10 p.Arg2957Gln Uncertain significance ★★ same type
DNAH10 p.Arg3955His Uncertain significance ★★ ⚠ same type
DNAH10 p.Asp3319Gly Uncertain significance ★★ ⚠ same type
DNAH10 p.Glu4042Gln Uncertain significance ★★ ⚠ same type
DNAH10 p.Gly4445Glu Uncertain significance ★★ same type
DNAH10 p.Ile4202Thr Uncertain significance ★★ same type

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/dnah10-p-ile4530phe (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown